Plasma Resistin Levels Research Articles

The effects of rosiglitazone and metformin on the plasma concentrations of resistin in patients with type 2 diabetes mellitus

Resistin is a protein secreted from adipose tissue that is thought to play a role in insulin sensitivity. We examined the effects of rosiglitazone and metformin on the plasma resistin levels in individuals with type 2 diabetes mellitus. Patients with type 2 diabetes mellitus who showed poor glycemic control with glimepiride (4 mg/d) were randomized to rosiglitazone (4 mg/d) and metformin (500 mg bid) treatment groups. All subjects continued glimepiride treatment as well. The plasma concentrations of resistin were measured at baseline and at 6 months of treatment for both groups. The anthropometric parameters, fasting plasma glucose, HbA1c, total cholesterol, triglyceride, high-density lipoprotein cholesterol, free fatty acids, and adiponectin concentrations were also measured. After 6 months of treatment, the reduction in plasma glucose levels was similar between the 2 groups. There were no significant changes in the lipid profiles of either group during the study period. The plasma resistin levels decreased in the rosiglitazone group (2.49 ± 1.93 vs 1.95 ± 1.59 ng/ml; P < .05) but increased in the metformin group (2.61 ± 1.69 vs 5.13 ± 2.81 ng/ml; P < .05). The plasma adiponectin concentrations were increased in the rosiglitazone group (2.91 ± 1.46 vs 4.23 ± 1.77 μg/ml; P < .05) but were unchanged in the metformin group. In summary, rosiglitazone treatment decreased the plasma resistin levels whereas metformin treatment increased them in patients with type 2 diabetes mellitus showing poor glycemic control with sulfonylurea therapy. These results suggest that the observed changes in plasma resistin levels are not the consequences of improved insulin resistance, nor are they consequences of glycemic control. Considering the potential role of resistin in insulin resistance, decrease in resistin levels may contribute to improving insulin action with rosiglitazone treatment.

Resistin Is an Inflammatory Marker of Atherosclerosis in Humans

Resistin, a plasma protein, induces insulin resistance in rodents. Recent reports suggest that circulating levels of resistin are elevated in obese and insulin-resistant rodents and humans. Whereas rodent resistin is made in adipocytes, macrophages are a major source of human resistin. Given the convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and atherosclerosis in humans. We examined whether plasma resistin levels were associated with metabolic and inflammatory markers, as well as with coronary artery calcification (CAC), a quantitative index of atherosclerosis, in 879 asymptomatic subjects in the Study of Inherited Risk of Coronary Atherosclerosis. Resistin levels were positively associated with levels of inflammatory markers, including soluble tumor necrosis factor-alpha receptor-2 (P<0.001), interleukin-6 (P=0.04), and lipoprotein-associated phospholipase A2 (P=0.002), but not measures of insulin resistance in multivariable analysis. Resistin levels also were associated (odds ratio and 95% confidence interval in ordinal regression) with increasing CAC after adjustment for age, sex, and established risk factors (OR, 1.23 [CI, 1.03 to 1.52], P=0.03) and further control for metabolic syndrome and plasma C-reactive protein (CRP) levels (OR, 1.25 [CI, 1.04 to 1.50], P=0.01). In subjects with metabolic syndrome, resistin levels further predicted CAC, whereas CRP levels did not. Plasma resistin levels are correlated with markers of inflammation and are predictive of coronary atherosclerosis in humans, independent of CRP. Resistin may represent a novel link between metabolic signals, inflammation, and atherosclerosis. Further studies are needed to define the relationship of resistin to clinical cardiovascular disease.

The Relation of Serum Adiponectin and Resistin Concentrations with Metabolic Risk Factors

Background: Adiponectin is a fat cell-secret ed cytokine, which has been reported to improve insulin sensitivity and have antiatherogenic properties. However, it is still unclear whether resistin plays a significant role in the development of insulin resistance in humans. The aim of this study was to investigate the relationship of the adiponectin and resistin concentrations with insulin resistance, metabolic markers and adiposity in healthy and type 2 diabetic subjects. Methods: Eighty-three type 2 diabetic and 139 healthy subjects were studied. Blood samples were drawn after fasting to determine the fasting plasma glucose, insulin, resistin, adiponectin, total cholesterol, triglyceride and HDL-cholesterol levels. The subcutaneous and visceral fat areas were measured at the umbilical level using computed tomography. Results: The serum adiponectin concentrations were significantly lower in the diabetic (6.7 ± 2.3 μg/mL) than in the obese (8.2 ± 2.4 μg/mL, P < 0.01) and non-obese subjects (9.9 ± 4.5 μg/mL, P < 0.01). The serum resistin concentrations were Similar between the non-obese, obese and type 2 diabetic subjects. From a multiple regression analysis, the fasting glucose, HDL-cholesterol and HOMA-IR were found to be independent determinants of the log of the adiponectin level in the diabetes group. In healthy subjects, the gender, BMI, HOMA-IR, visceral fat area and HDL-cholesterol wer e associated with the log of the adiponectin level. However, the log of the resistin level was n ot associated with the markers of insulin resistance and obesity. Conclusion: This study showed that the serum adiponectin concentration was closely related to the insulin resistance marker in both healthy and type 2 diabetic subjects. However, the resistin concentration was not associated with the markers of insulin resistance and/or obesity (J Kor Soc Endocrinol 20:444～451, 2005).

Adenovirus-mediated high expression of resistin causes dyslipidemia in mice.

The adipocyte-derived hormone resistin has been proposed as a possible link between obesity and insulin resistance in murine models. Many recent studies have reported physiological roles for resistin in glucose homeostasis, one of which is enhancement of glucose production from the liver by up-regulating gluconeogenic enzymes such as glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. However, its in vivo roles in lipid metabolism still remain to be clarified. In this study, we investigated the effects of resistin overexpression on insulin action and lipid metabolism in C57BL/6 mice using an adenoviral gene transfer technique. Elevated plasma resistin levels in mice treated with the resistin adenovirus (AdmRes) were confirmed by Western blotting analysis and RIAs. Fasting plasma glucose levels did not differ between AdmRes-treated mice and controls, but the basal insulin concentration was significantly elevated in AdmRes-treated mice. In AdmRes-treated mice, the glucose-lowering effect of insulin was impaired, as evaluated by insulin tolerance tests. Furthermore, total cholesterol and triglyceride concentrations were significantly higher, whereas the high-density lipoprotein cholesterol level was significantly lower. Lipoprotein analysis revealed that low-density lipoprotein was markedly increased in AdmRes-treated mice, compared with controls. In addition, in vivo Triton WR-1339 studies showed evidence of enhanced very low-density lipoprotein production in AdmRes-treated mice. The expressions of genes involved in lipoprotein metabolism, such as low-density lipoprotein receptor and apolipoprotein AI in the liver, were decreased. These results suggest that resistin overexpression induces dyslipidemia in mice, which is commonly seen in the insulin-resistant state, partially through enhanced secretion of lipoproteins.

Association of adiponectin and resistin with adipose tissue compartments, insulin resistance and dyslipidaemia

In this study, we investigated the association of plasma adiponectin and resistin concentrations with adipose tissue compartments in 41 free-living men with a wide range of body mass index (22-35 kg/m(2)). Using enzyme immunoassays, plasma adiponectin and resistin were measured. Intraperitoneal, retroperitoneal, subcutaneous abdominal and posterior subcutaneous abdominal adipose tissue masses (IPATM, RPATM, SAATM and PSAATM, respectively) were determined using magnetic resonance imaging. Total adipose tissue mass (TATM) was measured using bioelectrical impedance. Insulin resistance was estimated with the help of homeostasis model assessment (HOMA) score. In univariate regression, plasma adiponectin levels were inversely related to IPATM (r = -0.389, p < 0.05), SAATM (r = -0.500, p < 0.001), PSAATM (r = -0.502, p < 0.001), anterior SAATM (r = -0.422, p < 0.01) and TATM (r = -0.421, p < 0.01). In multiple regression models, adiponectin was chiefly correlated with PSAATM. Plasma adiponectin concentrations were also inversely correlated with HOMA score (r = -0.540, p < 0.001) and triglyceride (r = -0.632, p < 0.001), and positively correlated with high-density lipoprotein cholesterol (r = 0.508, p < 0.001). There were no significant correlations between resistin levels and adipose tissue masses, insulin resistance or dyslipidaemia. In men, total body fat is significantly correlated with plasma adiponectin, but not with plasma resistin levels. Low plasma adiponectin levels appear to be chiefly determined by the accumulation of posterior subcutaneous abdominal fat mass, as opposed to intra-abdominal fat, and are strongly predictive of insulin resistance and dyslipidaemia.

Impaired glucose tolerance is accompanied by decreased insulin sensitivity in tissues of mice implanted with cells that overexpress resistin

Resistin, the expression of which is suppressed by thiazolidinedione treatment in adipocytes, is one of the key molecules for the tight link between adiposity and insulin resistance. Here, we show the in vivo effects of resistin on insulin sensitivity in mature mice using a cell implantation method. Resistin cDNA was transfected into 3T3-L1 pre-adipocytes, which were then implanted into subcutaneous areas of nude mice. Metabolic analyses were performed 4 or 6 weeks after implantation. The mice implanted with 3T3-L1 cells overexpressing resistin (R-mice) showed significantly (p<0.05) increased plasma resistin levels. After a glucose load plasma insulin levels were significantly greater in R-mice than in mice implanted with mock-transfected cells (M-mice). The AUC of insulin after glucose loading was positively correlated with circulating resistin levels. Significantly decreased glucose responses after insulin injection were observed in R-mice, compared to M-mice. The insulin-induced phosphorylation level of IRS-1 was significantly lower in muscles of R-mice than M-mice. The expression of TNF-alpha mRNA in intra-peritoneal fat tissues was significantly greater in R-mice than in M-mice, but there was no difference between the two groups with regard to subcutaneous fat tissues. The concentration of TNF-alpha in plasma was positively correlated with resistin levels in R-mice. Resistin, when actually secreted from cells in mature mice, causes disturbed glucose metabolism, possibly based on decreased insulin sensitivity in muscle. The in vivo effects of resistin on insulin sensitivity might be in part mediated by increased TNF-alpha expression in visceral fat tissues.

Role of resistin in diet-induced hepatic insulin resistance

Resistin is an adipose-derived hormone postulated to link adiposity to insulin resistance. To determine whether resistin plays a causative role in the development of diet-induced insulin resistance, we lowered circulating resistin levels in mice by use of a specific antisense oligodeoxynucleotide (ASO) directed against resistin mRNA and assessed in vivo insulin action by the insulin-clamp technique. After 3 weeks on a high-fat (HF) diet, mice displayed severe insulin resistance associated with an approximately 80% increase in plasma resistin levels. In particular, the rate of endogenous glucose production (GP) increased more than twofold compared with that in mice fed a standard chow. Treatment with the resistin ASO for 1 week normalized the plasma resistin levels and completely reversed the hepatic insulin resistance. Importantly, in this group of mice, the acute infusion of purified recombinant mouse resistin, designed to acutely elevate the levels of circulating resistin up to those observed in the HF-fed mice, was sufficient to reconstitute hepatic insulin resistance. These results provide strong support for a physiological role of resistin in the development of hepatic insulin resistance in this model.

Role of resistin in diet-induced hepatic insulin resistance.

Resistin is an adipose-derived hormone postulated to link adiposity to insulin resistance. To determine whether resistin plays a causative role in the development of diet-induced insulin resistance, we lowered circulating resistin levels in mice by use of a specific antisense oligodeoxynucleotide (ASO) directed against resistin mRNA and assessed in vivo insulin action by the insulin-clamp technique. After 3 weeks on a high-fat (HF) diet, mice displayed severe insulin resistance associated with an approximately 80% increase in plasma resistin levels. In particular, the rate of endogenous glucose production (GP) increased more than twofold compared with that in mice fed a standard chow. Treatment with the resistin ASO for 1 week normalized the plasma resistin levels and completely reversed the hepatic insulin resistance. Importantly, in this group of mice, the acute infusion of purified recombinant mouse resistin, designed to acutely elevate the levels of circulating resistin up to those observed in the HF-fed mice, was sufficient to reconstitute hepatic insulin resistance. These results provide strong support for a physiological role of resistin in the development of hepatic insulin resistance in this model.

Plasma resistin, leptin and adiponectin levels in non‐diabetic and diabetic obese subjects

Plasma resistin, leptin and adiponectin levels in non‐diabetic and diabetic obese subjects

Adipokine levels in Cushing's syndrome; elevated resistin levels in female patients with Cushing's syndrome.

Cushing's syndrome (CS) is associated with central adiposity, insulin resistance and impaired glucose homeostasis. Adipose tissue is thought to regulates glucose homeostasis via circulating adipokines, such as resistin, leptin and adiponectin, although their role in the insulin resistance associated with CS has not been established. We examined the relationship between insulin resistance and adipokine levels in CS patients. We compared plasma levels of resistin, leptin and adiponectin in 10 women and four men patients with CS, with 14 health subjects matched for age, gender and body mass index. A subgroup of three women and four men with pituitary-dependent CS were re-examined at least 9 months after curative surgery. CS patients had significantly more truncal fat and less lean body mass as assessed by DEXA compared to control subjects. Total cholesterol, triglycerides and insulin resistance, as calculated using the homeostasis model assessment of insulin resistance (HOMA-R), was significantly increased in CS patients. Of the adipokines measured, only resistin was significantly different between female CS patients and female control subjects (5.05 +/- 0.56 vs. 2.91 +/- 0.39 micro g/l, P = 0.015). Curative surgery significantly reduced total body fat and truncal fat, leptin, total and low-density lipoprotein (LDL) cholesterol, glucose and HOMA-R. A reduction in both resistin and adiponectin was also observed but the differences between pre- and post-treatment levels did not achieve statistical significance. Here we report for the first time that resistin levels are significantly elevated in CS patients and may be important in the insulin resistance associated with glucocorticoid excess.

Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance.

Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.

Increased resistin blood levels are not associated with insulin resistance in patients with renal disease

Background:Resistin is a newly discovered insulin inhibitor secreted by adipocytes. We explored the potential role of resistin in the pathophysiological process of insulin resistance encountered in patients with renal disease. Methods:Resistin blood concentrations, insulin sensitivity index (by intravenous glucose tolerance test), and glomerular filtration rate (GFR; by inulin clearance) were assessed in 30 male patients with immunoglobulin A glomerulonephritis in different stages of renal disease. Results:Patients with increased resistin blood concentrations had more advanced renal failure and were significantly older. Plasma resistin levels correlated significantly with GFR (r = −0.82; P < 0.0001), plasma homocysteine concentration (r = 0.68; P < 0.001), and age (r = 0.42; P = 0.05), but not with fasted plasma insulin (r = −0.34; P = 0.12), glucose (r = 0.25; P = 0.19), and leptin (r = −0.24; P = 0.21) concentrations; body mass index (r = −0.06; P = 0.75), waist-hip ratio (r = 0.09; P = 0.63), or insulin sensitivity (r = −0.05; P = 0.79). In multiple regression analysis, GFR was the only independent predictor of plasma resistin concentrations in renal patients (r = −0.812; P < 0.0001). Conclusion:Resistin blood concentrations increase with progressive impairment of renal function. Thus, the kidney seems to be an important site of resistin elimination. However, the greater than 5-fold increase in resistin blood levels apparently is not associated with deterioration in insulin sensitivity in patients with renal disease.

Adiponectin is stimulated by adrenalectomy in ob/ob mice and is highly correlated with resistin mRNA.

Plasma levels of the adipocyte product adiponectin, a putative insulin-sensitizing agent, are reduced in obesity, whereas plasma levels of resistin, an agent that some believe to confer insulin resistance, are thought to increase with obesity. Because adrenalectomy can increase insulin sensitivity, we hypothesized that adrenalectomy would increase expression of adiponectin and decrease expression of resistin. Therefore, we measured adiponectin mRNA, adiponectin peptide, and resistin mRNA in adrenalectomized ob/ob mice. Adrenalectomy restored adiponectin expression in ob/ob mice to wild-type levels and stimulated adiponectin peptide to above wild-type levels. Surprisingly, expression of adiponectin and resistin was highly positively correlated even after statistical removal of effects of insulin, glucose, and adiposity. In addition, adiponectin and resistin expression were also highly correlated in diet-induced obese mice. The data support a role for adiponectin in mediating some effects of adrenalectomy on insulin sensitivity.